Classification of B-cell non-Hodgkin's lymphomas (NHL) : cytogenetic entities, immunopheneotype and clinical features

Antonio Cuneo

 

Dipartimento di Scienze Biomediche - Sezione di Ematologia
Università di Ferrara - Via Savonarola, 9 - 44100 FERRARA - ITALY
tel. int+39.0532.236978; fax: int+39.0532.212142; e-mail sse@dns.unife.it

February 2000

 

B-cell NHL include a number of clinicopathologic subsets of lymphoid neoplasms having heterogeneous features. This situation is reflected by variations in the classification systems that were proposed over the last decade. Cytogenetic findings were recognized to help defining a rationale biologic ground for the nosologic classification of lymphomas.

In this table an outlook of the salient cytogenetic entities in this spectrum of disorders is presented; a complete illustration of the cytogenetic profile of each disease is provided in specific cards. Unless otherwise specified the WHO classification system will be used.

 

Histologic subset and Immunophenotype

Putative cell of origin

Cytogenetic entitiy and corresponding clinical features

Small lymphocytic lymphoma (SLL)

Pan-B+; CD5+; CD23+; CD10-; sIgM+ faint

CD5+ virgin B-cell with germline IgV genes1

del(6)(q21-23) (20-30% of the cases)
  • Indolent disease; leukemic involvement by lymphoid cells, including prolymphocytes and/or paraimmunoblasts
  • Splenomegaly

Lymphoplasmacytic lymphoma

Pan-B+; CD5-; CD10-; cyIgM+

Peripheral B-lymphocyte transforming into plasma cell with mutated IgV genes and ongoing mutations

t(9;14)(p13;q32) PAX5/IgH (50% of cases)

  • Indolent low-grade disease, with possible clinical and/or histologic progression

Follicle centre cell lymphoma

Pan-B+; CD10+/-; CD5-; sIg+

Centrocytes / centroblasts of germinal centre origin with somatic hypermutation of the IgV genes and ongoing mutations (antigen driven stimulation)

t(14;18)(q32;q21) / BCL2 Rearr (70-80% of cases)
  • Indolent. Advanced stages predominate.
  • Conflicting data as to the prognostic significance of the t(14;18)/BCL2Rearr

Diffuse large cell lymphoma

CD19+; CD22+;

CD10-/+; SIg+

Large transformed B-cells harbouring somatic hypermutation of the Ig genes

(ongoing mutations in some cases)
  • Usually aggressive
  • Immunoblastic lymphoma (Kiel classification) do worse than centroblastic lymphomas
  • No convincing demonstration that any "primary" cytogenetic / molecular defect has prognostic significance; complex karyotype confers a shorter survival

Burkitt's lymphoma

Pan-B+; TdT-; CD10+; CD5-; sIgM+

Peripheral B-cells that have encountered the antigen and harbours somatic hypermutation of the Ig genes

t(8;14)(q24;q32) or variants /

  • Extremely aggressive disease
  • Specific treatment mandatory

Burkitt-like lymphoma Pan-B+; TdT-; CD10-/+ CD5-; sIg+

Peripheral B-cells that have encountered the antigen
  • Aggressive disease
  • Cases with dual 8;14 and 14;18 translocations have a worse outcome3

Mantle cell lymphoma

Pan-B +; CD5+;

CD23-; CD10-/+; sIgM+ bright

CD5+ B-cells of the follicle mantle having germline IgV gene sequences

t(11;14)(q13;q32) / BCL1 Rearr (50-90%4)
  • Advanced stages predominate
  • Response to chemotherapy often unsatisfactory
  • Short survival
  • Complex karyotype carries an unfavourable prognostic significance

Marginal zone B-cell lymphoma (MZBCL)

pan-B+; CD5-/+; CD10-; CD23-; CD11c+/-; cyIg + (40% of the cells), sIgM+ bright; sIgD-)

 Marginal zone lymphocytes harbouring hypermutated IgV genes

t(11;18)(q21;q21) / PI2 / MLT fusion (30-50% of the low-grade MALT)

Extra-nodal low-grade MALT lymphoma; indolent disease

t(1;14)(p21;q32)

  

Extra-nodal MALT lymphoma

del(7)(q22-31) (40% of the cases)

Splenic MZBCL

+3/+3q

(30-70% of the cases)

Nodal, extra-nodal and splenic MZBCL

Legend : +: positive in >90% of the cases; +/-: positive in more than 50% of the cases; -/+: positive in less than 50% of cases; -: positive in <10% of the cases; pan-B markers include CD19; CD20; CD79a; R = rearranged; sIg: surface immunoglobulins; cyIg: cytoplasmic Ig; IgV genes: genes encoding for the variable portion of the Ig.

Comments

  1. as was recently demonstrated to be the case with chronic lymphocytic leukemia, the leukemic counterpart of SLL, it is likely that part of the cases may derive from post-germinal centre quiescent B-cells that harbour hypermutated IgV genes;
  2. % variations depending on detection methods: molecular genetics and FISH more sensitive that conventional cytogenetics;
  3. data requiring confirmation (1 study only, see Macpherson et al., 1999);
  4. molecular genetic methods have limited application due to variability of breakpoints; FISH is the most sensitive technique.

Bibliography

Cytogenetic profile of lymphoma of follicle mantle lineage: correlation with clinicobiologic features.
Cuneo A, Bigoni R, Rigolin GM, Roberti MG, Bardi A, Piva N, Milani R, Bullrich F, Veronese ML, Croce C, Birg F, Döhner H, Hagemeijer A, Castoldi G
Blood. 1999 ; 93 (4) : 1372-1380.
PMID 9949181
 
The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas.
Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK, De Wolf-Peeters C, Hagemeijer A, Van den Berghe H, Marynen P
Blood. 1999 ; 93 (11) : 3601-3609.
PMID 10339464
 
World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (12) : 3835-3849.
PMID 10577857
 
Correlation of bcl-2 rearrangement with clinical characteristics and outcome in indolent follicular lymphoma.
López-Guillermo A, Cabanillas F, McDonnell TI, McLaughlin P, Smith T, Pugh W, Hagemeister F, Rodríguez MA, Romaguera JE, Younes A, Sarris AH, Preti HA, Lee MS
Blood. 1999 ; 93 (9) : 3081-3087.
PMID 10216105
 
Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma.
Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH, de Jong D, Maartense E, Schuuring E, Kluin PM
Blood. 1998 ; 92 (9) : 3152-3162.
PMID 9787151
 
Cellular origin of human B-cell lymphomas.
Küppers R, Klein U, Hansmann ML, Rajewsky K
The New England journal of medicine. 1999 ; 341 (20) : 1520-1529.
PMID 10559454
 
Small noncleaved, non-Burkitt's (Burkit-Like) lymphoma: cytogenetics predict outcome and reflect clinical presentation.
Macpherson N, Lesack D, Klasa R, Horsman D, Connors JM, Barnett M, Gascoyne RD
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (5) : 1558-1567.
PMID 10334544
 
t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with plasmacytoid differentiation.
Offit K, Parsa NZ, Filippa D, Jhanwar SC, Chaganti RS
Blood. 1992 ; 80 (10) : 2594-2599.
PMID 1384792
 
Genetics of small lymphocyte disorders.
Panayiotidis P, Kotsi P
Seminars in hematology. 1999 ; 36 (2) : 171-177.
PMID 10319386
 
Prognostic value of chromosomal abnormalities in follicular lymphoma.
Tilly H, Rossi A, Stamatoullas A, Lenormand B, Bigorgne C, Kunlin A, Monconduit M, Bastard C
Blood. 1994 ; 84 (4) : 1043-1049.
PMID 8049424
 
Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types.
Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ
Cell. 1999 ; 96 (1) : 35-45.
PMID 9989495
 
Written2000-02Antonio Cuneo
Section, Dept. Of Biomedical Sciences, University of Ferrara, 44100 Ferrara Italy
Updated2001-05David Gisselsson
of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

Citation

This paper should be referenced as such :
Gisselsson D
Classification of B-cell non-Hodgkin's lymphomas (NHL) : cytogenetic entities, immunopheneotype and clinical feature
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Deep/BNHLclassifID20012.htm
History of this paper:
Gisselsson, D. Chromosomal instability in cancer: Causes, consequences. Atlas Genet Cytogenet Oncol Haematol. 2001;5(3):236-243.
http://documents.irevues.inist.fr/bitstream/handle/2042/37771/05-2001-ChromosomInstabilID20023.pdf

Citation

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Classification of B-cell non-Hodgkin's lymphomas (NHL) : cytogenetic entities, immunopheneotype and clinical features

Online version: http://atlasgeneticsoncology.org/deep-insight/20012/meetings/js/lib/favicon/manifest.json